Suppression of sphingosine 1-phosphate lyase retards the liver regeneration in mice after partial hepatectomy

抑制鞘氨醇 1-磷酸裂解酶可延缓小鼠肝部分切除术后的肝脏再生

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作者:Yuko Kageyama, Baasanjav Uranbileg, Yoshika Kusumoto, Eri Sakai, Hitoshi Ikeda, Makoto Kurano, Yutaka Yatomi

Aim of the study

To examine whether SPL might play a stimulatory role in liver regeneration. Method: Using in-vivo siRNA technology, we inhibited SPL expression. Seventy percent of the liver was resected in mice as partial hepatectomy (PH). Liver tissue samples were collected and mRNA expression level of the SPL, IHC of the proliferating cell nuclear antigen (PCNA), protein levels of various proliferation factors and lipid measurements were performed in different groups.

Background

Liver regeneration is an extremely complicated process that is regulated by a number of signaling pathways. Sphingosine 1-phosphate (S1P), a potent bioactive lipid mediator playing crucial roles in various cellular responses through its receptors, has been attracting attention in the fields of hepatology, where S1P lyase (SPL), an irreversibly degrading enzyme of S1P, reportedly has a stimulatory role in growth of hepatocellular carcinoma (HCC).

Conclusion

We verified the importance of the SPL in liver regeneration, using the mice PH model. SPL might be a potential target to facilitate liver regeneration.

Results

The mRNA levels of SPL increased in PH mice on the third day after PH surgery. When we suppressed the expression of SPL by in-vivo siRNA, we observed a significant decline of the PCNA positive cell numbers. Furthermore, the Cyclin D1 expressions and phosphorylation of ERK also were decreased in the siSPL injected PH group.

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